A synbiotic combination of Lactobacillus gasseri 505 and Cudrania tricuspidata leaf extract prevents hepatic toxicity induced by colorectal cancer in mice

Abstract

Colorectal cancer (CRC) is known to be a life-threatening disease and commonly leads to metastasis in the liver. Fermented milk acts as an effective carrier for probiotic strains, whose consumption improves host health. Our previous study indicated that fermented milk that included a synbiotic combination of Lactobacillus gasseri 505 (505) and Cudrania tricuspidata leaf extract (CT) resulted in significantly greater anti-oxidative effects than fermented milk without CT. Therefore, we hypothesized that fermented milk containing CT and 505 (FCT) could result in hepatoprotective effects against CRC-induced liver metastasis. Liver inflammation and CRC were induced in male C57BL/6J mice, using azoxymethane/dextran sodium sulfate, and 505, CT, and FCT were administered to the 3 sample-treated 505, CT, and FCT groups, respectively, for 10 wk. The results showed that FCT treatment significantly reduced serum aspartate aminotransferase and alanine aminotransferase concentrations and elevated albumin concentrations. Moreover, the results of histological analysis showed that hepatic steatosis was notably reduced in the FCT group. Among the 3 sample-treated groups, the expression of mRNA associated with enzymes showing anti-oxidative activities, such as superoxide dismutase, catalase, and glutathione reductase, was the highest in the FCT-treated mice. In addition, FCT administration resulted in the greatest anti-inflammatory activity, as inflammatory marker levels (i.e., tumor necrosis factor-α, cyclooxygenase-2, myeloperoxidase, and nuclear factor kappa-light-chain enhancer of activated B cells) were significantly downregulated at the mRNA level and the expression of proteins associated with the nuclear factor kappa-light-chain enhancer of activated B cells and mitogen-activated protein kinase signaling pathways was suppressed by FCT. Therefore, this study demonstrated that fermented milk containing novel synbiotics has the potential to prevent hepatic toxicity induced because of CRC owing to its enhanced anti-oxidative and anti-inflammatory activities.

Keywords: Cudrania tricuspidata; Lactobacillus gasseri; colitis-associated colorectal cancer; hepatic toxicity; synbiotic.